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Multicluster Pcdh diversity is required for mouse olfactory neural circuit assembly
George Mountoufaris1,2, Weisheng V Chen1,2, Yusuke Hirabayashi2,3
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Science (New York, N.Y.)
|April 29, 2017
Summary
Vertebrate clustered protocadherins (Pcdh) from three gene clusters are crucial for olfactory sensory neuron (OSN) development. Their collective function ensures proper OSN axon targeting and self-avoidance in the olfactory bulb.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Vertebrate clustered protocadherins (Pcdh) are cell surface proteins encoded by three gene clusters: Pcdhα, Pcdhβ, and Pcdhγ.
- These proteins play roles in cell adhesion and neuronal wiring.
Purpose of the Study:
- To investigate the cooperative function of the three Pcdh gene clusters in the development of mouse olfactory sensory neurons (OSNs).
- To determine the necessity of Pcdh diversity for the correct assembly of OSNs into glomeruli in the olfactory bulb.
Main Methods:
- Analysis of Pcdh gene cluster deletions in mice.
- Assessment of OSN axonal arborization and self-avoidance.
- Experimental manipulation of Pcdh gene expression in OSNs.
Main Results:
- Deletion of individual Pcdh clusters had minor effects, but tricluster deletion caused severe defects in OSN axonal arborization and self-avoidance.
- Expression of a single Pcdh gene repertoire in OSNs prevented glomerular formation, indicating contact-mediated repulsion.
Conclusions:
- All three Pcdh gene clusters cooperate to generate the cell surface diversity essential for OSN targeting.
- Pcdh-mediated self-avoidance and target recognition are critical for proper olfactory system assembly.
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